1. Field of the Invention
The present invention relates to a tocopheryl phosphate, a salt thereof and a composition containing the tocopheryl phosphate or a salt thereof as a source of vitamin E for administration to animals, and to a method of supplying vitamin E to animals which comprises administering to animals the tocopheryl phosphate, a salt thereof or the composition containing the tocopheryl phosphate or a salt thereof. More specifically, the present invention relates to a tocopheryl phosphate, a salt thereof and a composition containing the tocopheryl phosphate or a salt thereof, capable of effectively supplying a source of vitamin E which has great effects on the prevention of aging of animals, the treatment or prevention of diseases, stress relief, increased hatchability, improved egg quality, the treatment or prevention of propagation disorder or mastitis, or reduction in the number of somatic cells in milk. The present invention also relates to a method of administering the tocopheryl phosphate, a salt thereof or a composition containing the tocopheryl phosphate or a salt thereof to animals.
2. Description of the Related Art
Vitamin E acts to prevent the production of peroxide lipid as a peroxide of an unsaturated fatty acid which is considered to be a material cause of the aging phenomenon, has a function of reinforcing blood vessels and activating the bloodstream, provides an anti-stress effect, and is a very important nutrient for human beings and other animals.
On the other hand, in stockbreeding, marine culturing or pet breeding, the problems of aging, reduced disease resistance, stress generation, decreased hatchability, deteriorated egg quality or meat quality, propagation disorder or mastitis, or reduction in the number of somatic cells in milk affect these animals, and a solution of these problems has hitherto been keenly demanded.
In the breeding of useful mammals including livestock animals such as cattle, pigs and horses, and pets such as dogs and cats, and experimental animals such as rats, mice and guinea pigs, reproduction is efficient because these animals are useful for human beings. As the breeding density increases, the acceleration of aging, reduced disease resistance, stress generation, accelerated oxidation of meat foods, deteriorated meat quality such as the blackening of meat foods, and propagation disorder occur more often. Propagation disorder is caused by premature birth, reduction of conception ratio, ovulatory retardation, embryo death, a weakened estrous symptom or reduced production of progesterone. Furthermore, when mastitis is generated, the number of somatic cells in milk increases and the commercial value of the milk is considerably lowered. For treating or preventing propagation disorder or mastitis, various vitamins, including vitamin E and derivatives thereof, and minerals have been conventionally added individually or in combination to the drinking water or feed and then fed to useful mammals.
Poultry such as domestic fowl, quail and turkey under overcrowded breeding conditions suffer from reduced disease resistance, stress generation, deteriorated meat quality and propagation disorder, and additionally, reduced egg quality in the case of egg layers. In order to overcome these problems, various vitamins, including vitamin E and derivatives thereof, and minerals have been conventionally added individually or in combination to the drinking water or feed and then fed to poultry.
Furthermore, in marine culturing, overcrowded breeding of marine animals causes aging problems, reduced disease resistance, stress generation, deteriorated meat quality, deteriorated egg quality and additionally, reduced hatchability and worsening body color. In order to overcome these problems, various vitamins, including vitamin E and a derivative thereof, and minerals have been conventionally added individually or in combination to the feed or premix and then fed to rainbow trout, sweet fish, carp, salmon, eel, yellow tail, globefish, flatfish, tuna, horse mackerel and prawn.
However, conventional vitamin E, a conventional derivative thereof or a combination with a mineral, when supplied to animals, cannot provide a sufficiently high effect on the treatment or prevention against aging, reduced disease resistance, stress generation, deteriorated meat quality, reduced hatchability, worsening body color, deteriorated egg quality, propagation disorder, mastitis or the generation of disease. Furthermore, vitamin E or the like is an oily substance having a high viscosity at room temperature and therefore, for example, it also has poor handleability. Under these circumstances, there has been a demand for the development of a vitamin derivative which provides, when applied to animals, a still higher effect on the treatment or prevention against aging, reduced disease resistance, stress generation, deteriorated meat quality, reduced hatchability, worsening body color, deteriorated egg quality, propagation disorder, mastitis or generation of disease, and which is easy to handle.
One problem which causes the low effects of conventional vitamin E or a conventional derivative thereof is that the natural .alpha.-tocopheryl most commonly used as a vitamin E source is expensive. The cost increases when it is used in admixture with the feed and accordingly, only a small dosage is fed to animals. Another problem is that natural .alpha.-tocopheryl or synthetic dl-.alpha.-tocopheryl has a good antioxidant capability but on the other hand, is itself easily oxidized. Accordingly, even if it is present in feed subjected to a heating process, it decomposes during the production or distribution process. As a result, the effect as vitamin E cannot be satisfactorily provided. Still another problem is that because .alpha.-tocopheryl and synthetic dl-.alpha.-tocopheryl or dl-.alpha.-tocopheryl acetate are oily substances having an extremely high viscosity at room temperature, they are incapable of uniform addition to feed or the like, are difficult to handle or are very cumbersome to use. Also, since they are insoluble in water, administration through the drinking water or by injection is not possible unless subjected to special processing such as emulsification. In order to overcome these problems, dl-.alpha.-tocopheryl acetate adsorbed to saccharides and formed into a powder or emulsified into a liquid product by an emulsifier is added to the feed or the like at present. The dl-.alpha.-tocopheryl acetate is relatively insusceptible to air oxidation and is stable, but has problems in that even if administered in vivo, the ester is not sufficiently converted into dl-.alpha.-tocopheryl. As a result, it fails to provide satisfactory effects as vitamin E. Also, it is difficultly absorbed into cells as compared to the dl-.alpha.-tocopheryl simple substance because it is an acetic ester compound. The dl-.alpha.-tocopheryl acetate emulsified into a liquid product by an emulsifier is bound to increase the cost because the ester is difficult to emulsify and has poor emulsification stability. Therefore, a special emulsifier is used.
A known specific example of the method of administering vitamin E to animals includes a method of supplying feed having added thereto vitamin E to egg layers to obtain eggs containing vitamin E (see, JP-B-63-50976, the term "JP-B" as used herein means an "examined Japanese patent publication").
However, the above-described conventional method for producing eggs containing vitamin E in high concentration has a problem in that the egg does not have a sufficiently high vitamin E content.
Taking into account these problems of the prior art, an object of the present invention is to provide a vitamin E source having a high absorption effect in animals, and which is easy to handle, is stable against heat and is capable of dissolving in water.
In order to achieve the above objectives, the present inventors have extensively investigated various vitamin E derivatives. As a result, they have found that dl-.alpha.-tocopheryl phosphate or a salt thereof, as one of vitamin E derivatives, is highly stable and useful because of its powder form at room temperature, provides a high vitamin E activity because it is readily absorbed into animal cells as compared with conventional dl-.alpha.-tocopheryl acetate, and can be an ideal vitamin E source due to its high biological activities available over a wide range of useful animals. Furthermore, the present inventors have verified that vitamin E is accumulated in an egg by adding .alpha.-tocopheryl phosphate or a salt thereof to the feed for egg layers.
Furthermore, the present inventors have found that a high-purity tocopheryl phosphate or a salt thereof having a tocopheryl phosphate purity of 95% or more and containing 5% or less P,P'-bistocopheryl diphosphate as an impurity has increased solubility in water in the neutral pH region as compared with tocopheryl phosphates having a low purity and can be easily administered to animals through drinking water or by injection. The present invention has been accomplished based on these findings.